OBJECTIVE: To investigate the safety and prognostic factors influencing the treatment of upper urinary tract urothelial carcinoma (UTUC) combined with bladder cancer (BCa) by laparoscopic simultaneous radical cystectomy and nephroureterectomy (RCNU). METHODS: The clinical data of patients admitted to Peking University Third Hospital for laparoscopic RCNU surgery from January 2009 to September 2023 were analyzed retrospectively. Based on the same gender, age (±5 years), history of uroepithelial tumors, underlying diseases, T-stage, N-stage, M-stage, American Society of Anesthesiologists (ASA) score, Charlson comorbidity index, and body mass index (BMI) (±5), 34 patients with RCNU were matched 1 ∶1 with patients with bladder cancer who underwent laparoscopic radical cystectomy (RC) alone. Kaplan-Meier survival analysis was used to calculate patient survival, and Cox proportional regression risk model was used to analyze clinical factors affecting prognosis. RESULTS: Of the 68 patients enrolled, the follow-up rate was 100% with a median follow-up time of 27.0 (11.7, 60.2) months. Comparison of intraoperative conditions (including operation time, estimated intraoperative bleeding, intra-operative blood transfusion, etc.) between the two groups of patients showed no significant difference (P>0.05). Comparison of preoperative creatinine and postoperative creatinine between the two groups of patients showed significant differences (P < 0.05). The perioperative Clavien grade Ⅲ-Ⅳ complication rates were 2.9% (1/34) in the RC group and 5.9% (2/34) in the RCNU group. There was no significant difference in terms of perioperative complications between the two groups. Overall survival was significantly lower in the patients receiving RCNU compared with the matched group receiving RC alone (P < 0.05). Cox regression analysis suggested that two factors, high N stage and high postoperative creatinine, were independent risk factors affecting the prognosis of patients in the 2 groups (P < 0.05). CONCLUSION The overall survival prognosis of patients undergoing RCNU surgery was worse compared with laparoscopic RC surgery alone during the same period. There was no clinically significant difference between the two groups in terms of operation time, intraoperative bleeding, and perioperative complications, and there were clinically significant differences in preoperative renal function and post-operative renal function.
Humans ; Laparoscopy/methods* ; Nephroureterectomy/methods* ; Cystectomy/methods* ; Prognosis ; Male ; Retrospective Studies ; Female ; Urinary Bladder Neoplasms/mortality* ; Middle Aged ; Aged

Objective: To investigate the effect of activation of the stimulator of interferon genes(STING) pathway on macrophage polarization function and its role in T-cell response. Methods: Mouse macrophage RAW264.7 cells were used.STING signaling related proteins in RAW264.7 macrophage treated with STING agonist diABZI were analyzed by Western blot,including TANK-binding kinase-1(TBK1),interferon regulatory factor-3(IRF3),STING,p-TBK1,p-IRF3,p-STING.The polarization of macrophage RAW264.7 cells treated with diABZI was analyzed by flow cytometry.Co-culture of diABZI-treated RAW264.7 macrophage and T cells was applied to evaluate the change of T cell response. Results: STING signaling related proteins were upregulated in macrophage RAW264.7 cells treated with diABZI for 3 hours.The expression of CD86 was upregulated on the surface of macrophages after 12 hours of diABZI treatment,and the CD86/CD206 ratio was elevated,which presented the M1 polarization phenotype.When coculturing diABZI-treated macrophage RAW264.7 cells with T cells,the cytokine secretion ability of T cells including CD4+T and CD8+T cells was enhanced and the expression of CD107a in CD8+T cells was upregulated. Conclusion STING signaling induces M1 polarization of macrophages which enhance the function of T cells,especially CD8+T cell immune response.

The new generation of artificial intelligence technology,represented by deep learning,has emerged as a crucial driving force in the advancement of new drug research and development.This article creatively proposes a workflow named"Molecular Factory"for the design and optimization of drug molecules based on artificial intelligence technology.This workflow integrates intelligent molecular generation models,high-performance molecular docking algorithms,and accurate protein-ligand binding affinity prediction methods.It has been integrated as a core module into DrugFlow,a one-stop drug design software platform,providing a comprehensive set of mature solutions for the discovery and optimization of lead compounds.Utilizing the"Molecular Factory"module,we conducted the research of second-generation inhibitors against Menin that can combat drug resistance.Through the integration of computational and experimental approaches,we rapidly identified multiple promising compounds.Among them,compound RG-10 exhibited the IC50 values of 9.681 nmol/L,233.2 nmol/L,and 40.09 nmol/L against the wild-type Menin,M327I mutant,and T349M mutant,respectively.Compared to the positive reference molecule SNDX-5613,which has entered Phase Ⅱ clinical trials,RG-10 demonstrated significantly enhanced inhibitory activity against the M327I and T349M mutants.These findings fully demonstrate the unique advantages of the"Molecular Factory"technology in practical drug design and development scenarios.It can rapidly and efficiently generate high-quality active molecules targeting specific protein structures,holding significant value and profound implications for advancing new drug discovery.

Objective To observe the drainage pathways of interstitial fluid(ISF)and substance clearance pattern in rat brain with fluorescence tracing imaging and treacer-based MRI.Methods Thirty-three male SD rats were randomly divided into fluorescence tracing group(F group,n=18)and treacer-based MRI group(MRI group,n=15),then further divided into thalamic,hippocampal and caudate nucleus subgroups,respectively.Evans blue was injected to rats in F group,and cardiac perfusion was performed after injection,then brain tissue was harvested,and frozen sections were made to observe the drainage pathways of IFS in different subgroups.MRI was performed on rats in MRI group before and after injection of gadolinium-diethylenetriamine pentaacetic acid(Gd-DTPA)to observe signal intensity in ROI of brain regions in different subgroups,the signal unit ratio was calculated,and the changing trend was explored.Results ISF in thalamus,hippocampus and caudate nucleus had different dominant drainage pathways,and the time of tracer reached to adjacent brain regions and whole brain in F group were different.In MRI group,within 4 h after injection of Gd-DTPA,there were differences in direction and clearance rate among tracer in thalamus,hippocampus and caudate nucleus,mainly manifesting as the tracer in thalamus and hippocampus drained to the ipsilateral cortex and lateral ventricle,while the tracer in the caudate nucleus diffused to the cortex and midbrain,and there were differences of the peak time of tracer signal among adjacent drainage brain regions.Conclusion Fluorescence and MR dual-mode imaging showed that there were differences in the dominant drainage pathways of IFS and clearance rates of small molecule substances among hypothalamus,hippocampus and caudate nucleus of rats.

Objective:To compare the patient-reported outcomes and short-term clinical outcomes between robotic-assisted and laparoscopic-assisted radical gastrectomy for locally advanced gastric cancer.Methods:This single-center prospective randomized controlled trial was conducted in the Department of Gastrointestinal Surgery, Affiliated Hospital of Qingdao University from October 2020 to August 2022. Patients with locally advanced gastric cancer who were to undergo radical gastrectomy were selected and randomly divided into two groups according to 1∶1, and received robotic surgery and laparoscopic surgery, respectively. Patient-reported outcomes and short-term clinical outcomes (including postoperative complications, surgical quality and postoperative short-term recovery) were compared between the two groups by independent sample t test, Mann-Whitney U test, repeated ANOVA, generalized estimating equation, χ2 test and Fisher′s exact test. Results:A total of 237 patients were enrolled for modified intention-to-treat analysis (120 patients in the robotic group, 117 patients in the laparoscopic group). There were 180 males and 59 females, aged (63.0±10.2) years (range: 30 to 85 years). The incidence of postoperative complications was similar between the robotic group and laparoscopic group (16.7% (20/120) vs. 15.4% (18/117), χ2=0.072, P=0.788). The robotic group had higher patient-reported outcomes scores in general health status, emotional, and social domains compared to the laparoscopic group, differences in time effect, intervention effect, and interaction effect were statistically significant (general health status: χ2 value were 275.68, 3.91, 6.38, P value were <0.01, 0.048, 0.041; emotional: χ2 value were 77.79, 6.04, 6.15, P value were <0.01, 0.014, 0.046; social: χ2 value were 148.00, 7.57, 5.98, P value were <0.01, 0.006, 0.048). However, the financial burden of the robotic group was higher, the differences in time effect, intervention effect and interaction effect were statistically significant ( χ2 value were 156.24, 4.08, 36.56, P value were <0.01, 0.043,<0.01). Conclusion:Compared to the laparoscopic group, the robotic group could more effectively relieve postoperative negative emotions and improve recovery of social function in patients.

Objective To explore the inhibitory effect of Sidaxue, a traditional Miao herbal medicine formula, on articular bone and cartilage destruction and synovial neovascularization in rats with collagen-induced arthritis (CIA). Methods In a SD rat model of CIA, we tested the effects of daily gavage of Sidaxue at low, moderate and high doses (10, 20, and 40 g/kg, respectively) for 21 days, with Tripterygium glycosides (GTW) as the positive control, on swelling in the hind limb plantar regions by arthritis index scoring. Pathologies in joint synovial membrane of the rats were observed with HE staining, and serum TNF-α and IL-1β levels were detected with ELISA. The expressions of NF-κB p65, matrix metalloproteinase 1 (MMP1), MMP2 and MMP9 at the mRNA and protein levels in the synovial tissues were detected using real-time PCR and Western blotting. Network pharmacology analysis was conducted to identify the important target proteins in the pathways correlated with the therapeutic effects of topical Sidaxue treatment for RA, and the core target proteins were screened by topological analysis. Results Treatment with GTW and Sidaxue at the 3 doses all significantly alleviated plantar swelling, lowered arthritis index scores, improved cartilage and bone damage and reduced neovascularization in CIA rats (P<0.05), and the effects of Sidaxue showed a dose dependence. Both GTW and Sidaxue treatments significantly lowered TNF-α, IL-1β, NF-κB p65, MMP1, MMP2, and MMP9 mRNA and protein expressions in the synovial tissues of CIA rats (P<0.05). Network pharmacological analysis identified MMPs as the core proteins associated with topical Sidaxue treatment of RA. Conclusion Sidaxue alleviates articular bone and cartilage damages and reduces synovial neovascularization in CIA rats possibly by downregulating MMPs via the TNF-α/IL-1β/NF-κB-MMP1, 2, 9 signaling pathway, and MMPs probably plays a key role in mediating the effect of Sidaxue though the therapeutic pathways other than oral administration.

Objective:To investigate the prognostic factors for all-cause mortality in patients with muscle-invasive bladder cancer(MIBC)with intermediate-to-high-risk primary prostate cancer.Methods:From January 2012 to October 2023,the clinical data of the patients with MIBC with intermediate-to-high-risk primary prostate cancer in Peking University Third Hospital were retrospectively analyzed.All the patients were monitored and the occurrence of all-cause death was documented as the outcome event in the prognostic study.Univariate and multivariate Cox proportional risk regression analysis models were implemented to search for independent influences on the prognosis of patients.For significant influencing factors(pathological T stage,M stage and perineural invasion of bladder cancer),survival curves were plotted before and after multifactorial Cox regression adjusting for confounding factors.Results:A total of 32 patients were included in this study.The mean age was(72.5±6.6)years;the median preoperative total prostate specific antigen(tPSA)was 6.68(2.47,6.84)μg/L;the mean preoperative creatinine was(95±36)μmol/L,and the median survival time was 65 months.The majority of the patients(87.5％)had high-grade bladder cancer,53.1％had lymphatic invasion,and 31.3％had perineural invasion.Prostate involvement was observed in 25.0％of the cases,and the positive rate of soft-tissue surgical margin was 37.5％.Multivariate Cox analysis revealed that preoperative creatinine level(HR=1.02,95％CI:1.01-1.04),pathological stage of bladder cancer T3(HR=11.58,95％CI:1.38-97.36)and T4(HR=19.53,95％CI:4.26-89.52)metastasis of bladder cancer(HR=9.44,95％CI:1.26-70.49)and perineural invasion of bladder cancer(HR=6.26,95％CI:1.39-28.27)were independent prognostic factors(P＜0.05).Survival curves with Log-rank test after adjusting for confounding factors demonstrated that bladder cancer pathology T3,T4,M1,and perineural invasion were unfavorable factors affecting the patients'survival prognosis(P＜0.05).Conclusion:Patients with MIBC with intermediate-to-high risk primary prostate cancer generally portends a poor prognosis.High preoperative serum creatinine,T3 or T4 pathological stage of bladder cancer,metastasis of bladder cancer and bladder cancer perineural invasion are poor prognostic factors for patients with MIBC with intermediate-to-high risk primary prostate cancer.

Objective:To summarize the clinical characteristics of patients with renal angiomyolipoma(RAML)combined with inferior vena cava(IVC)tumor thrombus,and to explore the feasibility of par-tial nephrectomy and thrombectomy in this series of patients.Methods:The clinical data of patients diagnosed with RAML combined with IVC tumor thrombus in the Department of Urology of the Peking University Third Hospital from April 2014 to March 2023 were retrospectively analyzed,and demographic and perioperative data of RAML patients with IVC tumor thrombus were recorded and collected from Elec-tronic Medical Record System,including age,gender,surgical methods,and follow-up time,etc.The clinical characteristics between classic angiomyolipoma(CAML)patients with IVC tumor thrombus and epithelioid angiomyolipoma(EAML)patients with IVC tumor thrombus were compared to determine the clinical characteristics of these patients.Results:A total of 11 patients were included in this study,in-cluding 7 patients with CAML with IVC tumor thrombus and 4 patients with EAML with IVC tumor thrombus.There were 9 females(9/11,81.8％)and 2 males(2/11,18.2％),with an average age of(44.0±17.1)years.9 patients(9/11,81.8％)experienced clinical symptoms,including local symp-toms including abdominal pain,hematuria,abdominal masses,and systemic symptoms including weight loss and fever;2 patients(2/11,18.2％)with RAML and IVC tumor thrombus did not show clinical symptoms,which were discovered by physical examination.Among the 11 patients,10 underwent radical nephrectomy with thrombectomy,of whom,3 underwent open surgery(3/10,30.0％),2 underwent laparoscopic surgery(2/10,20.0％),and 5 underwent robot-assisted laparoscopic surgery(5/10,50.0％).In addition,1 patient underwent open partial nephrectomy and thrombectomy.The patients with EAML combined with I VC tumor thrombus had a higher proportion of systemic clinical symptoms(100％vs.0％,P=0.003),more intraoperative bleeding[400(240,3 050)mL vs.50(50,300)mL,P=0.036],and a higher proportion of tumor necrosis(75％vs.0％,P=0.024)compared to the patients with CAML combined with I VC tumor thrombus.However,there was no statistically significant difference in operation time[(415.8±201.2)min vs.(226.0±87.3)min,P=0.053]between the two groups.Conclusion:Compared with the patients with CAML and IVC tumor thrombus,the patients with EAML and IVC tumor thrombus had a higher rate of systemic symptoms and tumor necrosis.In addi-tion,in the selected patients with CAML with IVC tumor thrombus,partial nephrectomy and tumor thrombectomy could be performed to better preserve renal function.

Objective:To analyze the epidemiological and clinical characteristics of children with acute brucellosis, providing reference for early diagnosis and standardized treatment of brucellosis in children.Methods:The data of 140 children with acute brucellosis at Xi'an Children's Hospital from April 2012 to October 2021 were collected. Their general information, epidemiological characteristics, clinical manifestations, laboratory and imaging examinations, treatment and prognosis were analyzed retrospectively.Results:Among 140 children with acute brucellosis, there were 78 males and 62 females, with a median age of onset and interquartile range of 3.4 (1.8, 5.8) years; 88.6% (124/140) of these children came from rural areas. The peak season for the onset of brucellosis was summer (47.1%, 66/140); 92.9% (130/140) had a confirmed epidemiological history; 7.9% (11/140) of the affected children were latent carriers. Among the 129 children with obvious clinical manifestations, fever accounted for 99.2% (128/129), hyperhidrosis accounted for 52.7% (68/129), and involvement of the reticuloendothelial system, joints, and nervous system accounted for 46.5% (60/129), 44.2% (57/129), and 6.2% (8/129), respectively, joint effusion accounted for 64.9% (37/57). All patients tested positive for tiger red plate agglutination test; 97.9% (137/140) of the patients had a serum tube agglutination test titer ≥1 ∶ 100. Positive blood culture accounted for 85.7% (120/140). The positive detection rate of serum tube agglutination test was higher than that of blood culture (χ 2 = 13.69, P < 0.001). Brucella was cultured from the cerebrospinal fluid of 8 children with concomitant encephalitis. The initial treatment plan for all children was oral compound sulfamethoxazole/doxycycline + rifampicin. In cases of arthritis, osteomyelitis or encephalitis, third-generation cephalosporins or meropenem were used intravenously at the same time. Dexamethasone was used for patients suffered from bilateral abductor nerve damage. All patients were cured without recurrence. Two cases had sequelae, namely introverted vision in the right eye and knee joint movement disorders. Conclusions:Most children with acute brucellosis have a confirmed epidemiological history and are mainly distributed in rural areas. The main clinical manifestation is fever, and joint involvement is also common. Standardized treatment can cure them.

Objective To observe the efficacy and safety of balloon occlusion hepatic arterial infusion chemotherapy(b-HAIC)for treating unresectable hepatocellular carcinoma(HCC)complicated with hepatic arterioportal fistula(HAPF).Methods Eight patients with unresectable HCC complicated with HAPF who underwent FOLFOX b-HAIC were retrospectively enrolled.The technical success rate and b-HAIC related adverse events were recorded,and the efficacy was evaluated.Results Totally 17 times b-HAIC were successfully performed in 8 cases,with technical success rate of 100%.One month after the first b-HAIC,shunt flow of HAPF decreased or even completely closed,with effective rate of 100%.After 2-3 times b-HAIC,the objective response rate(ORR)and disease control rate(DCR)of HCC was 87.50%(7/8)and 100%(8/8),respectively.Grade 1-3 adverse events were observed in all 8 cases,mainly presented as abdominal pain(7/8,87.50%)and transient elevation of transaminases and all alleviated after rest or symptomatic treatments.No grade 4-5 adverse event occurred.Conclusion b-HAIC was effective and relatively safe for treating unresectable HCC complicated with HAPF.